Stem cells have a capacity both for self-renewal and the generation of differentiated cell types. This pluripotentiality makes stem cells unique. In addition to studying the important normal function of stem cells in the regeneration of tissues, researchers have further sought to exploit the potential of in situ and/or exogenous stem cells for the treatment of a variety of disorders. While early, embryonic stem cells have generated considerable interest, the stem cells resident in adult tissues may also provide an important source of regenerative capacity.
These somatic, or adult, stem cells are undifferentiated cells that reside in differentiated tissues, and have the properties of self-renewal and generation of differentiated cell types. The differentiated cell types may include all or some of the specialized cells in the tissue. For example, hematopoietic stem cells give rise to all hematopoietic lineages, but do not seem to give rise to stromal and other cells found in the bone marrow. Sources of somatic stem cells include bone marrow, blood, the cornea and the retina of the eye, brain, skeletal muscle, dental pulp, liver, skin, the lining of the gastrointestinal tract, and pancreas. Adult stem cells are usually quite sparse. Often they are difficult to identify, isolate, and purify. Often, somatic stem cells are quiescient until stimulated by the appropriate growth signals.
Progenitor or precursor cells are similar to stem cells, but are usually considered to be distinct by virtue of lacking the capacity for self-renewal. Researchers often distinguish precursor/progenitor cells from stem cells in the following way: when a stem cell divides, one of the two new cells is often a stem cell capable of replicating itself again. In contrast, when a progenitor/precursor cell divides, it forms two specialized cells, neither of which is capable of replicating itself. Progenitor/precursor cells can replace cells that are damaged or dead, thus maintaining the integrity and functions of a tissue such as liver or brain.
Fibroblasts and smooth muscle cells (FSMCs) undertake diverse cellular functions during embryonic development and in steady state adult tissues and organs. Morphologically, they are often defined as elongated, spindle-shaped cells that readily adhere to tissue culture substrates and migrate over these substrates. However, FSMCs may exhibit a variety of shapes and sizes, depending on the host tissue and its physiological and pathological state. During the development of the internal organs, and their vasculature, FSMCs are the predominant cell types within both stroma and the vasculature's tunica media and adventitia, that are believed to be involved in the synthesis and remodeling of the extra cellular matrix (ECM), becoming relatively quiescent in the steady-state adult tissues.
Within the vascular system, FSMCs maintain vascular tone and function by expressing and secreting contractile and elastic proteins within the tunica media and adventitia. However, chronic activity by FSMCs impedes organ function. As an outcome, FSMCs are the principal cell types that can accumulate in diverse medical conditions, including tissue and organ fibrosis, atherosclerosis, and formation of atheromatous plaque after blood vessel injury. FSMCs may also contribute to the progression of cancer by serving as key cellular components in the tumor stroma, a finding that could implicate the tumor-associated FSMC as an important target for anti-cancer therapy.
Based on these similarities in morphology and function, fibroblasts and smooth muscle cells have been proposed to arise from a common lineage. Central to our understanding of fibroblasts and smooth muscle cells is the question of their origin. Several ideas have been proposed as serving a source of FSMCs for the adult thoracic and abdominal [coelomic] cavities and internal organs. The bone marrow, including hematopoietic stem cells [HSC], were initially presumed to contribute to FSMCs, and to continuously replenish the mesenchymal pool as part of normal tissue homeostasis; however it has been shown that HSCs in a variety of tissues only give rise to blood cells and platelets.
The mesothelium is an epithelial monolayer that lines the vertebrate's coelomic cavities and internal organs. The mesothelium provides a non-adhesive layer that facilitates the frictionless movements of organs within the coelomic cavity, through the secretion of phospholipids and their entrapment via abundant microvilli present on the serosal side, and protects the serosal surfaces from abrasion, infection, and tumor dissemination. By synthesizing and secreting a plethora of cytokines, chemokines and growth factors, the mesothelium reportedly performs many functions, including the control of fluid and solute transport, regulation of inflammation, hematopoiesis and wound healing.
The ability to manipulate tissue regeneration is of great interest for clinical and research purposes. Characterization of stem and progenitor cells having diverse development potential is therefore of great interest.